Numerous promising drug leads are regularly abandoned due to having poor pharmacokinetic profiles. Biomaterials are often used as drug delivery systems to improve the pharmacokinetics of these otherwise promising drug candidates. Hydrogels are a subset of biomaterials that offer porous matrices, permeable to endogenous nutrients in aqueous in vivo environments. Environmentally sensitive hydrogels have become of interest to further tailor these materials to only allow therapeutic release in response to specific environmental cues instead of simple encapsulation and subsequent diffusion. Enzyme-responsive materials allow for the exploitation of endogenous tissue enzyme expression levels and/or altered expression levels during pathological states. The simplest and most common method for stimulus-dependant release is through the destruction of the matrix to release encapsulated therapeutics that would otherwise be trapped indefinitely. A second approach is to covalently attach therapeutics to the hydrogel scaffold and include enzymatically sensitive cross linkages throughout the scaffold backbone. The third, and least common approach, is to use labile linkers between the therapeutic and the scaffold which affords controlled, precise release of the therapeutic with a known molecular structure. These linkers can also be tailored to specific enzymes that are elevated in certain disease states. This review will; 1) briefly describe matrix degradation; 2) present the cleavage of covalently attached therapeutics and; 3) highlight the few examples of targeted cleavage of therapeutics from specific matrix locations and the potential use of these systems in biomedicine.

Self-assembly is the spontaneous organization of small components into higher-order structures facilitated by the collective balance of non-covalent interactions. Peptide-based self-assembly systems exploit the ability of peptides to adopt distinct secondary structures and have been used to produce a range of well-defined nanostructures, such as nanotubes, nanofibres, nanoribbons, nanospheres, nanotapes, and nanorods. While most of these systems involve self-assembly of α-peptides, more recently β-peptides have also been reported to undergo supramolecular self-assembly, and have been used to produce materials—such as hydrogels—that are tailored for applications in tissue engineering, cell culture and drug delivery. This review provides an overview of self-assembled peptide nanostructures obtained via the supramolecular self-assembly of short β-peptide foldamers with a specific focus on N-acetyl-β³-peptides and their applications as bio- and nanomaterials.

We describe a new class of hydrogelator based on helical β³-peptide foldamers carrying a bioactive payload. The β³-peptides self-assemble to form a nanofibrous mesh resulting in a stable hydrogel. Co-incubation with different β³-peptide monomers allowed tuning of cell adherence.

A popular strategy to control cellular growth and differentiation is the employment of self-assembling peptides as biomaterials. In this study we decorated ultrashort helical N-acetylated β-tripeptides with cell adhesion signals IKVAV and RGD, which spontaneously self-assemble to give nanofibres with multiple signals, and form a bioscaffold that supports the growth of cells.

Ischaemic stroke remains one of the leading causes of death and disability worldwide, without any long-term effective treatments targeted at regeneration. This has led to developments of novel, biomaterial-based strategies using self-assembling peptide hydrogels.